High level of gene expression in mammalian cells has always been a challenge to production of a large amount of proteins for diagnostic or therapeutic uses. A typical process for protein production involves with the steps of 1) transfecting a vector comprising a gene of interest into mammalian cells such that the vectors may randomly incorporate into sites of chromosomes of the cells through recombination and 2) screening and selecting cells expressing a high level of expression of the gene of interest. Random recombination renders protein production as an art in science, rather a predictable, repeatable scientific process. Additionally, the large amount of selection work is also a costly, burdensome, unpredictable process. Therefore, there is a great need in the art to incorporate genes of interest into predictable, specific sites on chromosomes and reach a high level of gene expression.